A number of operative procedures require the use of metal screws, nails, plates, fasteners, rods, pins, wire structures, suture anchors and staples to aid in the reconstruction of bone fractures, torn ligaments and other injuries as well as for closing wounds. Balloon-expandable coronary stents find use in the treatment of coronary artery disease by providing an alternative to balloon angioplasty and bypass surgery. Stents are thin walled tubular-shaped devices which counteract significant decreases in vessel or duct diameter by supporting the conduit by a mechanical scaffold. In addition to stenting coronary arteries, stenting is widely used in other natural body conduits, such as central and peripheral arteries and veins, bile ducts, esophagus, colon, trachea or large bronchi, ureters, and urethra.
Long-term implants can have damaging effects on the body and, where applicable, some may need to be eventually removed, thus requiring surgery. Certain implants including stents cannot be removed at all. Permanent metal implants can increase the risk of infection due to the presence of a foreign material in the body.
To alleviate undesired side effects of implants, medical device manufacturers have developed biodegradable materials that can be absorbed by the body over time. These biodegradable implants, also referred to as in-vivo degradable, absorbable, resorbable, bioresorbable and bioabsorbable, are made of various materials that will diminish in mass over time within the body. Essentially, once biodegradable material implants such as stents, sutures, staples, plates or screws have aided in healing the injury or the medical condition and are no longer required, they slowly degrade/dissolve in the body, eliminating the need for removal surgery.
“Permanent implants” are typically made of stainless steel, cobalt alloys or nickel-titanium alloys. Fracture fixation devices are relatively thick (200 microns to 5 mm) and are placed using conventional open surgery. Other implants such as stents are implanted in the “radially collapsed state” by a catheter which is inserted at an easily accessible location and then advanced through the vasculature to the deployment site. Once in position, the stent is deployed by inflation of a dilation balloon. Stents have a relatively thin wall thickness (50 to 200 microns) and, as remote insertion is used for their placements, stents need to be visualized with X-ray based fluoroscopy procedures.
“Permanent stents” which remain in place indefinitely cause problems if multiple stents or restenting is required as they are impossible to remove and can cause in-stent restenosis. According to the American Heart Association the two main benefits of intracoronary stents are (i) the treatment of dissections and (ii) the prevention of restenosis; these benefits are realized during the first few months after implantation. Coronary dissections are effectively contained by stent insertion and undergo a healing process, with the majority of cardiac events occurring in the first six months. Stent prevention restenosis also occurs within the first six months. Therefore, a stent that is in place beyond six months has no clear function and “temporary stents” such as biodegradable stents offer the same near term benefits as “permanent stents” without the potential risk for long-term complications. Furthermore, the use of biodegradable stents enables multiple stenting and restenting.
“Biodegradable stents” have been proposed to address a short-term need for a stent. A first approach was to use biodegradable polymers and the first biodegradable stents were implanted in animals in 1988. A polymer of poly-L-lactide was used which could withstand up to 1,000 mm Hg of crush pressure and kept its radial strength for one month. The stent was almost completely degraded after nine months. Biodegradable stents made of polyglycolic acid were evaluated in canines in the early 1990s. Unfortunately, during the absorption process most polymers cause inflammation leading to severe intimal hyperplasia or thrombotic occlusions. This is overcome in the present invention by including a biodegradable metallic material as a principal stent constituent.
Stinson in U.S. Pat. No. 5,980,564 (1999) U.S. Pat. No. 6,174,330 (2001), Jodhav in U.S. Pat. No. 6,991,647 (2006) and Flanagan in US 2007/0050009 describe biodegradable polymeric stents.
While polymer based biodegradable stents have received most attention, metal based biodegradable stents have been developed as well. Magnesium alloy-based stents have been tested in animals and humans. The Lekton Magic coronary stent is laser cut from an absorbable magnesium alloy tube. Alloy composition is used to modulate the time required for complete biocorrosion and dissolution times range from one day to two months. As magnesium is one of the most important micronutrients, degradation products are not expected to have any side effects. Magnesium stents, however, are radiolucent causing difficulties with detection of stent embolization, confirmation of complete stent expansion and apposition with precise placement of overlapping stents. These disadvantages can be overcome in the present invention by using iron and/or zinc as a principal stent constituent for a stent.
Harder in US US20040098108A1 (2004) describes intraluminal endoprostheses such as stents, comprising a carrier structure which contains a magnesium alloy of the following composition by weight: magnesium: >90%, yttrium: 3.7%-5.5%, rare earths: 1.5%-4.4% and balance: <1%. The balloon-expandable carrier structure is cut by a laser from a precursor tube.
Heublein in US20020004060A1 (2002) discloses metallic medical implants. After fulfilling its temporary support function, the implant degrades by corrosion at a predetermined rate. Negative long-term effects are thus avoided. The use of metals provides superior mechanical properties. The corrosion rate of the implant is set by the appropriate choice of materials. The main constituent is selected from the group consisting of alkali metals, alkaline earth metals including magnesium, iron, zinc and aluminum. The biological, mechanical and chemical properties of the materials can be beneficially affected if a subsidiary constituent is provided in the form of manganese, cobalt, nickel, chromium, copper, cadmium, lead, tin, thorium, zirconium, silver, gold, palladium, platinum, rhenium, silicon, calcium, lithium, aluminum, zinc, iron, carbon or sulfur. The preferred material is either an alloy of magnesium with a content of up to 40% lithium plus addition of iron, or an iron alloy with a small amount of aluminum, magnesium, nickel and/or zinc. Suitable corrosion rates are achieved by an alloy or a sintered metal made of approximately equal parts of zinc and iron.
Bolz in U.S. Pat. No. 6,287,332 (2001) describes implantable bioresorbable vessel wall supports, especially coronary stents using a combination of metals which decompose in the human body without any harmful effects. The combination of metallic materials is designed such that the material of the vessel wall support dissolves at a certain decomposition rate and without the production of bio-incompatible decomposition products. For correspondingly uniform corrosion to be obtained, such an alloy comprises a component selected from one or several metals of the group consisting of magnesium, titanium, zirconium, niobium, tantalum, zinc and silicon which covers itself with a protective oxide coating. For uniform dissolution of the mentioned oxide coating to be attained, a second component is added to the alloy, possessing sufficient solubility in blood or interstitial fluid, such as lithium, sodium, potassium, calcium, iron or manganese. The combination of a passivating and a soluble component ensures a timely and uniform decomposition into biocompatible breakdown products. The corrosion rate can be regulated through the ratio of the two components.
Loffler in US 2008/0103594 (2008) describes absorbable medical implant composites comprising a matrix made of a crystalline magnesium containing bio-corrosive alloy. The implant is reinforced either with bio-corrosive alloy fibers selected from the group consisting of magnesium, calcium, iron and yttrium or non-biodegradable fiber materials. Suitable reinforcements include amorphous or nanocrystalline fibers made by melt-spinning, which, compared to crystalline materials, provide increased strength and delayed in-vivo corrosion.
Generally stents are formed by a two step process, namely (i) drawing of a suitable tube precursor followed by (ii) suitably perforating it into the desired stent pattern i.e. by laser cutting. Alternative fabrication methods include direct forming e.g. using electroforming or sputtering.
Hines in U.S. Pat. No. 6,019,784 (2000) describes a process for electroforming an expandable stent by (i) coating an electrically-conductive mandrel with a suitable resist material, (ii) exposing the resist to an appropriate light pattern and frequency so as to form a stent pattern in the resist, (iii) electroplating the mandrel with a suitable stent material and (iv) etching away the temporary mandrel once a sufficient layer of stent material is deposited, leaving a completed stent. According to Hines a suitable stent material is selected for biocompatibility and mechanical characteristics. It must be sufficiently ductile to be radially expandable to form an appropriate intra vascular endoprosthesis and sufficiently rigid to hold its shape once the expansion force is removed. It must also be sufficiently inert to be biocompatible and resistant to etching solutions. Gold and various gold alloys generally satisfy these requirements because they are generally inert and resistant to corrosion from bodily fluids and, also are resistant to a wide variety of etching solutions. Other metals which have specific beneficial characteristics as stent materials include silver, nickel, platinum, rhodium, palladium, iron and various alloys of these metals. It is anticipated that high gold, platinum, or nickel alloys with from about 95 to about 100 percent content of such metals would produce stents with highly desirable characteristics. Selection of particular materials for the stent is based primarily upon biocompatibility and mechanical characteristics.
The use of biodegradable metallic implants for the reconstruction of bone fractures and or closing wounds has a long history as demonstrated below.
Stroganov in U.S. Pat. No. 3,687,135 (1972) describes magnesium alloys for use in fracture fixation. Magnesium-based alloys are disclosed which provide high mechanical strength, do not result in vigorous gas-evolution and have a rate of absorption which is slower than the process of bone consolidation.
Kuttler in US20060020289 describes biocompatible and bioabsorbable suture and clip material for surgical purposes comprising biodegradable magnesium alloys which can remain in the wound as the suture and clip material is absorbed by the body and which, by virtue of their compositions, improve protection from wound infections and promote the healing process.
The employment of grain-refinement to specifically enhance mechanical properties of metallic materials has been described as demonstrated below.
Erb in U.S. Pat. No. 5,352,266 (1994), and U.S. Pat. No. 5,433,797 (1995) describes a process for producing nanocrystalline metals, particularly nanocrystalline nickel. Nanocrystalline materials are electrodeposited onto the cathode in an aqueous acidic electrolytic cell by application of a pulsed current to produce wear resistant coatings, magnetic materials and catalysts for hydrogen evolution.
Palumbo in US Patent Application Publication No. US 2005-0205425 A1 discloses a process for forming coatings or free-standing deposits of nanocrystalline metals, metal alloys or metal matrix composites at high deposition rates. The process employs tank, drum plating or selective plating processes.
Tomantschger in U.S. Ser. No. 12/003,224 filed Dec. 20, 2007 describes means for electroplating metallic materials with varying properties in a single plating cell including fine-grained, coarse grained and amorphous metals and alloys.
Segal in U.S. Pat. No. 5,400,633 (1993) discloses a method for deformation processing of metals by extrusion through a die assembly with two channels having equal cross sectional areas under near frictionless conditions and in U.S. Pat. No. 7,096,705 (2006) Segal describes a shear-extrusion method of severe plastic deformation for the fabrication of metal shapes with ultra-fine microstructures. These method have been identified as being suitable for achieving grain-refinement in metals and alloys.